1. Field of the Invention
A basic factor in life is the ability of a vertebrate to distinguish between self and foreign proteinaceous materials. The mammalian immune system relies on the fact that within a short time after birth, defense mechanisms have been elaborated which permit the destruction and neutralization of foreign invading bodies, particularly microorganisms. A prerequisite of this system is its ability to make fine distinctions between differences in primary, secondary, and tertiary structure of proteins.
A significant industry has developed in using the mammalian ability to produce antisera specific for one or more epitopic sites to quantitatively determine a particular compound. In order to produce the antisera, it is necessary to hyperimmunize a mammal with an antigen, so that antibodies are produced which specifically bind to the epitopic sites of the antigen. In many instances, the isolation of the antigen in sufficient amounts can be arduous, in addition to the difficulties involved in purifying the antigen. In some instances, there may be an interest in having antibodies for a specific determinant or epitopic site of an antigen having a plurality of determinant sites.
In the subject invention, there is a further interest in providing an antigenic oligopeptide capable of competing with an antigen determinant site for antisera. In the production of vaccines, where an attenuated virus is injected into a host to induce an immunological response, there are serious problems concerned with the preparation of such vaccines, side effects resulting from the injection of such vaccines, and the potential for the vaccine to induce the disease from which the host was to be protected by the injection. It would therefore be desirable to be able to mimic with a relatively short oligopeptide one or more determinant sites of an infectious virus, where the oligopeptides could serve to initiate the immune response, but otherwise would have no deleterious effects.
One viral disease which has been a major problem in public health and transfusion practice is hepatitis, resulting from hepatitis B virus (HBV) infection. Worldwide research of this problem has led to the development of a variety of vaccines using the hepatitis B surface antigen (HBsAg). Vaccines used in the current clinical trials of vaccines against HBV infections have been most often derived from the plasma of HBV-infected blood donors. The safety and efficacy of such vaccines which use natural viral products must be tested by one-time innoculation of colony bred chimpanzees. Because susceptible chimpanzees are not easily available, and the same chimpanzee cannot be used more than once, the testing of the vaccine can be subject to the availability of a susceptible chimpanzee. In addition, the long term effects of the viral products are not known adequately and alternative approaches to vaccine development warrant serious consideration.
There is therefore ample incentive to develop vaccines which would not require the rigorous monitoring and testing required in the use of the naturally occurring antigens.
2. Brief Description of the Prior Art
The following references give an historical background toward efforts in understanding hepatitis antigen. Vyas and Shulman, Science, 170 332 (1970); Rao and Vyas, Nature New Biology, 241 240 (1973); Rao and Vyas, Microbios (1974) 9, 239; Rao and Vyas, ibid. (1974) 10, 233; Peterson et al. PNAS USA 74 1530 (1977); Vyas et al. ed., Viral Hepatitis Proceedings of UCSF Symposium, Franklin Institute Press, Philadelphia (1978); Valenzuela et al. Nature, 280 815 (1979); Charnay et al., Nucleic Acid Res. 7 355 (1979).